Hepatitis A is a disease which sporadically breaks out through oral infection with HAV. However, recent reports on its large-scale epidemic have become rare in advanced countries, because in those countries hygienic environment has been improved as a whole. Nevertheless, there is a report stating that 1 to 1.5% of patients suffering from acute hepatitis A become fluminant and, therefore, hepatitis A is believed to be a disease worth notice, epidemiologically and clinically.
Recently, the number of people having anti-HAV antibody has been reduced year by year as the number of the reports on the epidemic has been reduced. As a result, most of people not more than 35-year-old are negative in anti-HAV antibody in the advanced countries. However, there become conspicuous, cases where such antibody-negative young people take passage to regions highly infected with indigenous hepatitis A and get infected. Taking into consideration the recent tendency that many enterprises branch out into the developing countries and that chances of traveling abroad have been increased, a preventive vaccine has been required to be immediately developed. However, any of such vaccines have not yet been put into practical use.
On the other hand, hepatitis B is a disease caused by the infection with hepatitis B virus (hereunder referred to as "HBV") through blood or body fluid. Its prognosis is not good and this disease frequently shifts to chronic hepatitis, cirrhosis and even hepatocellular carcinoma. Until now, an effective means for treating hepatitis of this type has not yet been developed. Under such circumstances, a hepatitis B vaccine derived from plasma of the carriers has first been developed as a preventive means. Moreover, to overcome the difficulty in securing starting material, which is caused by the lack of the carrier plasma, there has recently been developed a technique comprising inserting a structural gene of HBs antigen, into yeast or animal cells as host cells in accordance with a genetic recombination technique to cause the expression, producing a large amount of only HBs antigen as a source material for vaccines for preventing the hepatitis, and purifying it to obtain highly purified antigen.
It is believed that the number of hepatitis B carriers is about two hundred million in the world and that in the HAV indigenous regions such as Southeast Asia and Africa, the number of carriers almost reaches 10 to 15% of their population. This clearly shows highly latent possibility of HBV infection in the HAV indigenous regions. Therefore, in such regions, a means for preventing infection associated with hepatitis A virus and with hepatitis B virus has been eagerly requested to be developed.
Recently, there have been actively conducted many attempts for developing vaccines capable of preventing a plurality of objective diseases through only one inoculation, i.e., polyvalent vaccines (combined vaccines) for the purposes of decreasing the number of inoculations, hence decreasing accidents possibly happening during its inoculation and reducing cost in preparing vaccines, when the vaccines are produced as a means for preventing various infectious diseases. However, such mixing sometimes reduces the immunogenicities of the vaccines (interference action). Now, this becomes a major obstacle in developing a polyvalent vaccine.